CHAPTER 186 – AKAP Signaling Complexes: The Combinatorial Assembly of Signal Transduction Units

Understanding the molecular organization of intracellular signaling pathways is a topic of considerable research inter-est. Multiprotein signaling complexes create focal points of enzyme activity to disseminate the intracellular action of many hormones and neurotransmitters. The spatio-temporal activation of protein kinases and/or phosphatases is important in controlling where and when phosphorylaton events occur. Anchoring proteins and targeting subunits provide a molecular framework that orients protein kinases and phosphatases toward selected substrates. Prototypic examples of these "signal-directing molecules" are A-kinase anchoring proteins (AKAPs) that sustain multi-component signaling complexes of the cAMP dependent protein kinase (PKA) and G proteins and other enzymes. These protein-protein interactions not only focus PKA toward certain substrates but also spatially segregate parallel signaling pathways.